Protein variants including alternatively processed and misfolded proteins have been associated with many different human diseases. For example, misfolded protein aggregates play a critical role in many devastating human diseases including Alzheimer's (AD) and Parkinson's diseases, diabetes and cancer. However, assessing the variant's role in the onset and progression of different diseases is hampered by a lack of reagents that can distinguish between protein isoforms in vivo. Development of such reagents has been hindered by two main factors: protein variants often occur at only trace levels in vivo and the variants may differ only subtly from the parent form, making them difficult to separate and purify. Novel separation technologies that can tease apart subtle protein variants along with novel molecular recognition protocols are needed to create reagents with sufficient specificity to distinguish between these protein variants. Therefore, there is a continuing need for technologies capable of generating highly selective reagents to specific protein isoforms isolated from mammalian tissue.